Transcriptomics

Dataset Information

18

Age-associated Changes in Basal NF-κB Function in Human CD4+ T Lymphocytes via Dysregulation of PI3 Kinase (dataset 2)


ABSTRACT: Immune impairment and high circulating level of pro-inflammatory cytokines are landmarks of human aging. However, the molecular basis of immune dysregulation and the source of inflammatory markers remain unclear. Here we demonstrate that in the absence of overt cell stimulation, gene expression mediated by the transcription factor NF-κB is higher in purified and rested human CD4+ T lymphocytes from older compared to younger individuals. This increase of NF-κB -associated transcription includes transcripts for pro-inflammatory cytokines such as IL-1 and chemokines such as CCL2 and CXCL10. We demonstrate that NF-κB up-regulation is cell-intrinsic and mediated in part by phosphatidylinositol 3-kinase (PI3K) activity induced in response to metabolic activity, which can be moderated by rapamycin treatment. Our observations provide direct evidence that dysregulated basal NF-κB activity may contribute to the mild pro-inflammatory state of aging. Peripheral blood mononuclear cells (PBMCs) were isolated from heparinized blood using Ficoll-Paque Plus density gradient centrifugation. CD4+ T cells were obtained by positive selection using anti-human CD4 microbeads. After a 4h incubation at 37ºC (5% CO2 incubator), cells were harvested and collected by centrifugation. Total cellular RNA was prepared using Qiagen RNeasy protocols. Labeling and amplification were done with the standard Illumina protocol, and the biotin-labeled cRNA was hybridized to Illumina's HumanHT-12 v4 Expression BeadChip. The arrays were washed, blocked and the biotin-labeled cRNA was detected by staining with streptavidin-Cy3. Samples were divided into 2 age groups, young and old, with the cut off at 65 years and above as old.

ORGANISM(S): Homo sapiens  

SUBMITTER: Karen Madara  William H Wood III   Kevin G Becker   Arsun Bektas   Luigi Ferrucci   Elin Lehrmann   Ranjan Sen   Yongqing Zhang    

PROVIDER: E-GEOD-62332 | ArrayExpress| 2015-01-09

SECONDARY ACCESSION(S): GSE62332PRJNA263936

REPOSITORIES: GEO, ArrayExpress

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Publications

Age-associated changes in basal NF-κB function in human CD4+ T lymphocytes via dysregulation of PI3 kinase.

Bektas Arsun A   Zhang Yongqing Y   Lehmann Elin E   Wood William H WH   Becker Kevin G KG   Madara Karen K   Ferrucci Luigi L   Sen Ranjan R  

Aging 20141101 11


Immune impairment and high circulating level of pro-inflammatory cytokines are landmarks of human aging. However, the molecular basis of immune dys-regulation and the source of inflammatory markers remain unclear. Here we demonstrate that in the absence of overt cell stimulation gene expression mediated by the transcription factor NF-κB is higher in purified and rested human CD4+ T lymphocytes from older compared to younger individuals. This increase of NF-κB -associated transcription includes t  ...[more]